Drug abuse plays a prominent role in the HIV epidemic in Russia; nearly 80% of cases are attributed to injection drug use. A history of drug use or continued use after an HIV diagnosis can lead to negative health consequences. Drug use may hinder efforts to engage patients in medical care including use of antiretroviral treatment (ART). A direct physiologic impact of drugs of abuse on HIV disease progression has not been clearly documented despite immunologic findings suggesting a rational basis for such an association. Hence, a variety of factors associated with drug use may place the HIV-infected drug user at increased risk for more rapid HIV disease progression. However, clear evidence of an independent association between drug abuse and HIV disease progression awaits further study. The primary goal of this research initiative is to investigate the relationship between drug abuse and HIV disease progression by utilizing a currently developing cohort of 700 HIV-infected adults in Russia, many with a prior history of injection drug use. This 1-year R21 pilot study, "Drug Use IMPACT" (Investigating and Measuring Progression to AIDS in a Cohort Trial), will lay important groundwork for the design of a future longitudinal research initiative that can more definitively assess the relationship between drug use and HIV disease progression. The Specific Aims are: 1. Use an existing cohort of HIV-infected Russians to assess markers of HIV disease progression (i.e., CD4 cell count, HIV viral load [HIV RNA]) and confounding factors. 2. Estimate the effect size of drug use on markers of HIV disease progression, controlling for ART use, baseline CD4 cell count, HIV RNA (for CD4 outcome), alcohol use, depression, and sociodemographics. 3. Explore potential mechanisms by which drug use worsens HIV disease progression (e.g. reduced access to ART, increased alcohol use, depression, and HCV co-infection). We will recruit 100 subjects from an existing NIH study and collect additional self-report data on medication adherence and drug use. We will collect biological samples to assess CD4 cell count, HIV RNA, and drug use (urine toxicology on all and hair toxicology on a subsample). These data will be combined with data already available on the cohort (e.g. alcohol use, demographics). We hypothesize that illicit drug use is independently associated with more rapid HIV disease progression, as measured by CD4 cell count and HIV viral load. The data generated from this study will allow us to conduct preliminary tests of this hypothesis. Specifically, it will provide important effect size estimates that will be useful for designing a future cohort study that follows subjects longitudinally over several years to fully characterize the relationship between drug abuse and HIV disease progression. The primary analysis will be on any current drug use; however, the effects of specific drug use characteristics (i.e., specific drug, route of administration, exposure duration) will be explored in secondary analyses. Evidence suggests a relationship between drug use and worse HIV disease progression but the study of this relationship in the United States is complicated by several important confounders: unknown individual duration of HIV infection in an epidemic three decades old; substance use that frequently involves multiple drugs; longstanding use of ART with associated viral resistant strains; and common ART use which has a dominant effect on HIV disease progression. Each of these confounders is mitigated in the current Russian setting, making it a promising site to examine both the association between drug use and HIV disease progression, and the potential pathways that may mediate such a relationship. Elucidation of the relationship of drug use to HIV disease progression will facilitate efforts by clinicians, public health professions, and policy makers to improve the medical care, addiction treatment, and ultimately the health status of HIV-infected drug users. [unreadable] [unreadable] [unreadable]